EP3807286B1 - Degradable silane having thio and amino groups, silicic acid polycondensates and hybrid polymers produced therefrom, use thereof and method for producing the silanes - Google Patents

Description

The present invention relates to new silanes and the production of biodegradable, organically modifiable silicic acid polycondensates (resin systems) and polymers thereof or therewith. The silanes according to the invention contain one or more substituents bonded to the silicon via oxygen and having short or longer hydrocarbon chains, with longer chains being interrupted either by hydrolyzable and/or enzymatically or otherwise cleavable groups within these chains and/or substituted in such a way that when they are cleaved Groups the remaining hydrocarbon chains are water soluble. These substituents also contain thiol and/or amine groups. The silanes can be condensed inorganically and/or linked organically via an addition reaction with compounds having C=C double bonds or rings (“X” radicals). The reaction of silanes with several thiol and/or amino groups and of condensates of the silanes according to the invention with compounds with two or more CC double bonds and/or rings leads to polymerization products. According to the invention, the reaction partners with the radicals X also contain short or longer hydrocarbon chains, with longer chains being interrupted either by hydrolyzable and/or enzymatically or otherwise cleavable groups within these chains and/or substituted in such a way that when these groups are cleaved, the remaining hydrocarbon chains are water-soluble . They can be purely organic materials (monomers or oligomers) or condensed silane-based systems. The addition reaction or polyaddition/polymerization of thiol or amine and ene/ring-opening component can be carried out, for example, thermally or redox-induced or by irradiation with visible and/or UV light. This results in possible processing methods for the production of structured materials, e.g. 2 or multi-photon polymerization (2PP; MPP), the digital light processing method (DLP), stereolithography (STL), multi-jet modeling (MSM), Poly Jet Printing (PJP), Ink Jet, UV Lithography, Nanoimprint and Screen Printing. The materials obtained in this way and to a large extent also their precursors are stable to irradiation with γ-rays, so that they can be sterilized. By varying the proportion of inorganically crosslinkable units and/or of organically polymerizable/polyaddable units, the mechanical properties of the hybrid polymers produced from the silanes can be specifically adjusted so that they resemble those of natural, soft or hard tissue. They can be colonized by cell types such as endothelial cells and are therefore suitable, for example, as scaffolds for stabilizing and growing cells or tissue. When stored in buffers, the hybrid polymers decompose to a greater or lesser extent within a few weeks, with the formation of toxically harmless, mostly water-soluble, small-scale degradation products.

Due to the increasing life expectancy of people in Germany and the resulting undersupply of required donor organs, alternatives to organ transplantation from donor to recipient are urgently needed. Already in the 1990s the idea for so-called tissue engineering came up. This interdisciplinary field has set itself the goal of improving or replacing the function of damaged tissue, ideally in order to grow entire replacement organs and tissue from the patient's own material. In order for cells to form functioning three-dimensional structures outside the body, they need a supporting matrix, which is realized in tissue engineering using artificial scaffold structures. This can either be seeded in vitro with cells, which then grow, multiply and ultimately form tissue that is then transplanted, or used directly in the body at the site to be treated to support regrowth of the surrounding tissue. In both cases, it is advantageous if the scaffold degrades over time, making room for tissue formation. For this reason, materials are primarily sought that are broken down and excreted by the body over time. In addition to tissue engineering, biodegradable polymers are also used as drug delivery systems for long-term medication, resorbable sutures or implants, e.g. B. used for fixation after fractures.

However, the biodegradable polymers used to date are not free from disadvantages. Natural polymers are very expensive, have no tunable degradation rates, and only limited mechanical properties that can be tuned. In addition, they can provoke defensive reactions of the body and/or do not provide good cell adhesion, which is necessary for tissue formation. Some species, such as PLA and PGA, become acidic products such as B. lactic and glycolic acid hydrolyzed, which also catalyze the further polymer degradation (autocatalysis), which is why it is difficult to predict. Furthermore, these products can also cause inflammatory reactions.

There are numerous methods for producing scaffolds. In order to produce highly complex structures, three-dimensional objects can now be built up from several layers with the aid of computer-generated designs ( computer-aided designs , CAD). Processes that make use of this technique are referred to as rapid prototyping or solid free-form processes. With these methods, anatomically adapted scaffolds can be generated based on computed tomography (CT) or magnetic resonance imaging (MRI) data. Stereolithography is often used. In this technique, photopolymerization is initiated by electromagnetic radiation. A special case of stereolithography is two -photon polymerization (2PP). With this technique, ultra-fine structures can be generated with high resolution.

To adequately mimic the ECM (the extracellular matrix) for tissue engineering , scaffolds of biopolymers generated by 2PP are good from a chemical point of view suitable. When using degradable scaffold materials, dismantling the scaffold also offers the opportunity to create space for cell migration and expansion.

Materials that can be used in medical technology have been sought for a long time, which can be structured in a targeted manner and which are biodegradable despite the polymerization of organic groups that has taken place, in particular of (methacrylate and other) C=C double bonds. Among other things, biodegradable organically polymerizable hybrid polymers were considered for this purpose. These are usually modifications of known ORMOCER ^® s, ie hydrolytically condensed silane compounds that carry organically crosslinkable groups. Some such ORMOCER ^® s have already been described as inherently biocompatible. Hybrid materials that are at least partially biodegradable under physiological conditions have also been reported. R.Houbertz et al. showed in Coherence and Ultrashort Pulse Laser Emission, 2010, 583 and in WO 2011/098460 A1 biocompatible materials that can be structured by 2PP. These either contain residues attached via Si-C bonds which carry organically polymerizable groups, or they are produced from a mixture of silanes with Si-C-bonded, organically polymerizable residues and organically polymerizable compounds. These materials have been shown to be to some extent hydrolytically biodegradable and capable of being colonized by cells.

Obel et al. were able to integrate the organic residues containing polymerizable groups into the hybrid polymer structure by introducing a hydrolytically cleavable Si-OC bond in such a way that a largely degradable material is obtained after polymerization. As can be seen from examples of WO 2016/037871 A1 results, such structured materials suffer weight loss in water as well as in buffers such as PBS. Using NMR spectroscopy, the hydrolytic cleavage of the structure at all cleavable points and thus the degradation of the material could be demonstrated. The partially degradable materials can be colonized by cells.

The organic crosslinking of the materials takes place according to WO 2016/037871 A1 usually through the construction of polymethacrylate chains. These are not broken down during the hydrolytic splitting of the materials and therefore remain in the breakdown product.

EP 0 779 890 A1 discloses silanes in which radicals having at least one carbon atom are attached to the silicon atom and their use in the preparation of organically modified silicic acid polycondensates.

The object of the present invention is to provide crosslinkable and crosslinked materials which, on the one hand, are accessible to a closer crosslinking or are more closely crosslinked than purely organic materials and can therefore achieve mechanical properties that can essentially only be adjusted with silicon-containing hybrid materials that on the other hand, however, can be more completely degraded under physiological conditions than the previously known hybrid materials, in particular the presence of longer, poorly cleavable and thus poorly degradable chain structures such as polymethacrylate chains should be avoided. If possible, the materials according to the invention should also be sterilizable and biocompatible, so that they are suitable for the production of implants or scaffolds.

figure 1 shows a 3D shaped body made of a material according to the invention and printed with the aid of Digital Light Processing (DLP method). figure 2 shows a porous molding printed by the same method, also made of material according to the invention.

The present invention is defined in the appended claims.

• bereit, wobei
• die Gruppe R¹ oder jede der Gruppen R¹ unabhängig voneinander
  • über ein Sauerstoffatom an das Silicium gebunden ist,
  • eine geradkettige oder verzweigte kohlenwasserstoffhaltige Kette mit mehreren Strukturelementen aufweist, die jeweils nicht mehr als 8 aufeinander folgende Kohlenstoffatome besitzen, wobei die kohlenwasserstoffhaltige Kette aus Alkyleneinheiten aufgebaut ist, deren Glieder unsubstituiert oder substituiert sind, wobei die Substituenten unter Hydroxy-, Carbonsäure-, Phosphat-, Phosphonsäure-, Phosphorsäureester-, tertiären Aminogruppen und Aminosäuregruppen ausgewählt sind, und die kohlenwasserstoffhaltige Kette innerhalb der einzelnen Elemente weiterhin durch Sauerstoffatome, Schwefelatome oder Sulfonylgruppen unterbrochen sein kann, wobei jedes der Strukturelemente der kohlenwasserstoffhaltigen Kette durch eine Estergruppe als spaltbare Gruppe vom nächsten Strukturelement getrennt ist,
  • mindestens eine Thiol- oder eine primäre oder sekundäre Aminogruppe aufweist,
• die Gruppe R oder jede der Gruppen R unabhängig voneinander eine hydrolytisch kondensierbare Gruppe ist, die unter Alkyl-COO-, Alkyl-O- und HO- ausgewählt ist, und
• a 1, 2, 3 oder 4 ist.

In particular, the present invention provides a silane of formula (1)

^R1a _{SiR4 -a} (1)

• ready, whereby
• the group R ¹ or each of the groups R ¹ independently
  • is bonded to the silicon via an oxygen atom,
  • has a straight-chain or branched hydrocarbon-containing chain with a plurality of structural elements, each of which has no more than 8 consecutive carbon atoms, the hydrocarbon-containing chain being composed of alkylene units whose members are unsubstituted or substituted, the substituents being hydroxy, carboxylic acid, phosphate , Phosphonic acid, phosphoric acid ester, tertiary amino groups and amino acid groups are selected, and the hydrocarbon-containing chain within the individual elements can also be interrupted by oxygen atoms, sulfur atoms or sulfonyl groups, each of the structural elements of the hydrocarbon-containing chain being separated from the next structural element by an ester group as a cleavable group is,
  • has at least one thiol or one primary or secondary amino group,
• the group R or each of the groups R is independently a hydrolytically condensable group selected from alkyl-COO-, alkyl-O- and HO-, and
• a is 1, 2, 3 or 4.

In addition, the present invention provides an organically modified silicic acid polycondensate comprising a hydrolytic condensation product of a silane according to the invention or a mixture of several of these silanes.

In addition, the present invention provides an organically modified, polymerized silicic acid polycondensate, which can be prepared by reacting the silane according to the invention and/or an organically modified silicic acid polycondensate according to the invention with a compound R ² (X) _b (2), in which the group R ² has a b-fold binding Hydrocarbon skeleton having a straight or branched hydrocarbon-containing chain having one or more structural elements each having not more than 8 consecutive carbon atoms, each of several structural elements of the hydrocarbon-containing chain being separated from the next structural element by a cleavable group, the cleavable groups being selected are under ester, anhydride, amide, carbonate, carbamate, ketal, acetal, disulfide, imine, hydrazone and oxime groups, X is a group which in said reaction with the at least one Thiol or primary or secondary amino group of the radical R ¹ of the silane of formula (1) undergoes an addition reaction, and b is 2, 3, 4 or greater than 4.

In addition, the present invention provides the use of the organically modified, polymerized silicic acid polycondensate according to the invention in the form of a shaped body as a biologically or medically useful object or as an object for cell or tissue stabilization or for cell or tissue cultivation.

The thiol or primary or secondary amino group is a polyaddable group.

Preferably, in the silane of formula (1), at least one or each of the groups R ¹ consists exclusively of organic moieties.

In the silane of formula (1), the at least one thiol or primary or secondary amino group is preferably located at the non-silicon end of the R ¹ group, or, in the case of branched chains, at least at one non-silicon end of the R ¹ group.

The number of elements having features (a) and (b) in a group R ¹ is preferably two to ten, more preferably two to six.

In the silane of the formula (1), at least one of the elements of the hydrocarbon skeleton of the radical R ¹ preferably has a maximum of six, preferably not more than four and particularly preferably not more than three consecutive carbon atoms. It is particularly preferred that all elements of the hydrocarbon skeleton of the radical R ¹ have a maximum of three consecutive carbon atoms. This can apply to all R ¹ radicals, so that only elements of the hydrocarbon structure with a maximum of three consecutive carbon atoms are present in the R ¹ radicals in the silane.

Preferably, in the silane of formula (1), each R group is a hydrolytically condensable group and/or alkyl, provided that at least one R group is a hydrolytically condensable group and no more than one R group is an alkyl group.

Preferably, in the silane of formula (1), a is 2 or, when a plurality of such silanes are mixed, an average of about 2.

In the organically modified, polymerized silicic acid polycondensate, the element or at least one of the elements of the hydrocarbon-containing chain of the radical R ² preferably has a maximum of six, more preferably no more than four and particularly preferably no more than three consecutive carbon atoms.

The compound (2) preferably contains no silicon.

The number of elements in a group R ² is preferably two to ten, more preferably two to six.

The reactants of the reaction, ie the silane or the polycondensate on the one hand and the compound R ² (X) _b on the other hand, can be used in any ratio to one another. The compound R ² (X) _b can be used in the stoichiometric excess or in excess of the silane or the polycondensate, or in the same amount, based on the groups that react with one another. If, for example, a complete implementation of the polyaddable groups, e.g. B. the thiol groups, desired in the silane or polycondensate, the compound R ² (X) _b can be added in excess. However, if, for example, no complete implementation of the polyaddable groups, e.g. B. the thiol groups, desired in the silane or polycondensate, the compound R ² (X) _b can be added in deficit. In this way, some of the polyaddable groups are not converted and can then be used for later attachment of molecules, e.g. B. enzymes, or only increase the solubility in a medium by the polarity of the groups, for example.

In one embodiment, unreacted polyaddable groups of the silane or polycondensate are present in the organically modified, polymerized silicic acid polycondensate, e.g. B. thiol groups.

In another embodiment, in the organically modified, polymerized silicic acid polycondensate, all polyaddable groups of the silane or polycondensate, e.g. B. thiol groups have been implemented.

The compound R ² (X) _b serves as a crosslinker and is thus preferably a small molecule. The molecular weight is preferably at most 3000 g/mol, more preferably at most 2000 g/mol and most preferably at most 1000 g/mol. In certain embodiments, the compound has a molecular weight of at most 500 g/mol.

This low molecular weight compound R ² (X) _b preferably contains no silicon.

An organically modified, polymerized silicic acid polycondensate is preferred, in which the silicon-free compound R ² (X) _b has a molecular weight of at most 3000 g/mol and the ratio of the groups X of the compound (2) to the sum of the thiol and amino groups in the silanes (1) and condensation products thereof is from 0.1 to below 1.0.

The organically modified, polymerized silicic acid polycondensate according to the invention can also contain at least one filler, preferably selected from tricalcium phosphate, hydroxyapatite, bioglass and magnesium particles.

The present invention differs from the subject matter of WO 2016/037881 A1 . In the process of WO 2016/037881 A1 the C=C double bonds are contained in the silane or the polycondensate. Such C = C double bonds are z. B. contained in acrylates. When reacting with a thiol, the thiol must be used in excess so that no unreacted and therefore toxic acrylate remains. After the reaction, the excess thiol must be washed out. In contrast, in the present invention, the thiol is contained in the silane or the polycondensate. If the acrylate-containing crosslinker is added in deficit, it is completely converted. Subsequent removal of unreacted crosslinker is not required.

1. (1) In dem Verfahren der WO 2016/037871 A1 muss das Thiol im Überschuss zugegeben werden, damit toxisches Acrylat vollständig umgesetzt wird. Dadurch ist das Verfahren der WO 2016/037871 A1 grundsätzlich eingeschränkt. Diese Einschränkung gilt für die vorliegende Erfindung nicht.
2. (2) Da Thiol nicht im Überschuss zugegeben werden muss, entfällt das Entfernen des überschüssigen Thiols nach der Reaktion.
3. (3) Durch Einsatz eines Unterschusses an Vernetzer, z. B. Acrylat, kann eine unerwünschte intramolekulare Vernetzung vermieden werden.
4. (4) Die Reaktionsreihenfolge von Kondensation und nachfolgender Polymerisation ist im Vergleich zu WO 2016/037871 A1 weniger eingeschränkt. Wenn zuerst kondensiert und dann polymerisiert wird, werden aufgrund von sterischen Behinderungen möglicherweise nicht alle im Polykondensat enthaltenen polymerisierbaren Gruppen umgesetzt. Im Fall der vorliegenden Erfindung ist dies jedoch nicht problematisch, da die im Polykondensat enthaltene polyaddierbare Gruppe ein nicht-toxisches Thiol ist, während es im Fall von WO 2016/037871 A1 ein toxisches Acrylat sein kann.
5. (5) Als Vernetzer kann in der vorliegenden Erfindung auch eine voluminöse cyclische Gruppe, die C=C-Doppelbindungen enthält, eingesetzt werden. Umgekehrt wäre eine solche voluminöse cyclische Gruppe als Bestandteil eines Polykondensats aus sterischen Gründen problematisch und würde zudem die Viskosität übermäßig erhöhen.
6. (6) Wenn der acrylathaltige Vernetzer im Unterschuss zugegeben wird, verbleiben in dem Polykondensat nicht-umgesetzte Thiole. Diese können die Polarität und damit die Kompatibilität mit einem wässrigen Medium erhöhen, oder sie können eine geeignete Funktionalisierung darstellen, um weitere Gruppen, z. B. bioaktive Subtanzen wie Enzyme, an das fertige Produkt, also das polymerisierte Polykondensat, zu binden.
7. (7) In der vorliegenden Erfindung kann als Ausgangsverbindung Siliciumtetraacetat eingesetzt werden. Die Verwendung dieser Verbindung führt bei der organischen Modifizierung zu einer nahezu vollständigen Umesterung und ist daher vorteilhaft. Die hydrolytische Kondensation wird dann im Gegensatz zum Stand der Technik bei erhöhter Temperatur, beispielsweise bei 90 °C, durchgeführt (vgl. Beispiel C), um aus dem Siliciumtetraacetat die Acetatgruppen vollständig abzuspalten. Dies ist vorteilhaft, da verbleibende Acetatgruppen sauer reagieren und damit zelltoxisch sind. Die Verwendung von Siliciumtetraacetat ist also nur möglich, wenn die hydrolytische Kondensation bei erhöhter Temperatur erfolgen kann. Da Acrylate, welche temperaturempfindlich sind, nicht in den Silanen, sondern im Vernetzer enthalten sind, kann die hydrolytische Kondensation bei erhöhter Temperatur durchgeführt werden. Im Gegensatz dazu sind in den Silanen des Standes der Technik Acrylate enthalten, wodurch der Einsatz einer erhöhten Temperatur und damit die Verwendung von Siliciumtetraacetat ausgeschlossen sind.

These fundamental differences result in the following advantages (1) to (7) of the present invention:

1. (1) In the proceedings of WO 2016/037871 A1 the thiol must be added in excess so that the toxic acrylate is completely converted. As a result, the procedure is WO 2016/037871 A1 basically restricted. This limitation does not apply to the present invention.
2. (2) Since thiol does not have to be added in excess, there is no need to remove the excess thiol after the reaction.
3. (3) By using a deficit of crosslinkers, e.g. B. acrylate, unwanted intramolecular crosslinking can be avoided.
4. (4) The reaction order of condensation and subsequent polymerization is compared to WO 2016/037871 A1 less restricted. When condensing first and then polymerizing, not all of the polymerizable groups contained in the polycondensate may be reacted due to steric hindrances. In the case of the present invention, however, this is not a problem since the polyaddable group contained in the polycondensate is a non-toxic thiol, while in the case of WO 2016/037871 A1 can be a toxic acrylate.
5. (5) As a crosslinking agent in the present invention, a bulky cyclic group containing C=C double bonds can also be used. Conversely, such a bulky cyclic group as part of a polycondensate would be problematic for steric reasons and would also increase the viscosity excessively.
6. (6) If the acrylate-containing crosslinker is added in deficit, unreacted thiols remain in the polycondensate. These can increase polarity and thus compatibility with an aqueous medium, or they can provide suitable functionalization display to show other groups, e.g. B. bioactive substances such as enzymes to bind to the finished product, ie the polymerized polycondensate.
7. (7) In the present invention, silicon tetraacetate can be used as the starting compound. The use of this compound leads to almost complete transesterification in the organic modification and is therefore advantageous. In contrast to the prior art, the hydrolytic condensation is then carried out at elevated temperature, for example at 90° C. (cf. example C), in order to completely split off the acetate groups from the silicon tetraacetate. This is advantageous since remaining acetate groups react acidically and are therefore cytotoxic. The use of silicon tetraacetate is therefore only possible if the hydrolytic condensation can take place at elevated temperature. Since acrylates, which are temperature-sensitive, are not contained in the silanes but in the crosslinker, the hydrolytic condensation can be carried out at elevated temperatures. In contrast, the silanes of the prior art contain acrylates, which means that the use of an elevated temperature and thus the use of silicon tetraacetate are ruled out.

If a is greater than 1, the radicals R ¹ in the silane of the formula (1) can be the same or different. If 4-a is greater than 1, the R radicals can be the same or different.

The bond between R ¹ and the silicon atom can be configured as a CO-Si group or as a C(O)-O-Si group. R ¹ is thus to be addressed in the former case as an alkoxy radical and in the latter case as an acyloxy radical.

As defined above, the hydrocarbyl chain of R ¹ must have no more than 8 consecutive carbon atoms, preferably less than 8. When the total is 8 or less than 8, the presence of a cleavable group is optional. If the number is greater, there must be cleavable groups which interrupt the hydrocarbon-containing chain(s) in such a way that no more than 8, but preferably even fewer, carbon atoms follow one another. Even with a total of at most 8 carbon atoms in the hydrocarbon-containing chain, this can optionally (and preferably) be subdivided into smaller elements by cleavable groups. The shorter the element or elements made up of hydrocarbon groups, the better the degradability, because the shorter fragments are formed during degradation.

The hydrocarbon-containing chain of R ¹ is preferably made up of alkylene units. Their members can, but do not have to, be substituted with one or more substituents, the substituents preferably being selected from hydroxy, carboxylic acid, phosphate, phosphonic acid, phosphoric acid ester, tertiary amino groups and amino acid groups.

The hydrocarbon-containing chain of R ¹ can also be interrupted within the single element or the individual elements by oxygen atoms (ether groups), sulfur atoms (thioether groups) or sulfonyl groups (-S(O) ₂ -).

The cleavable groups of R ¹ are ester groups.

In a first particularly preferred embodiment, the silane is one that has two or, in the case of a mixture of several silanes, about two acyl radicals per silicon and two or about two radicals R ¹ .

In an embodiment which can be combined with this or is independent thereof, the radical R ¹ is an alkoxy radical which is substituted by a thiol group and preferably has 2 to 6 carbon atoms. The thiol group may be at the non-silicon end of R ¹ ; instead, a non-terminal CH ₂ group can be substituted with the thiol group, this residue preferably being located as far away from the silicon atom as possible.

In an alternative embodiment which can be combined with or is independent of the first particularly preferred embodiment, the radical R ¹ is branched and has two thiol groups which are preferably located at the ends of R ¹ which are remote from the silicon.

In a further embodiment which can be combined with or is independent of the first particularly preferred embodiment, the radical R ¹ is straight-chain; its hydrocarbon chain has 4 to 20 carbon atoms. This chain is interrupted by one or more ester groups (-C(O)O-, which can point in either of the two possible directions); the individual elements formed in this way can also be interrupted by sulfur and/or oxygen atoms. A thiol group is preferably located at the non-silicon end of the chain. This thiol group can be the only thiol group or one of several thiol groups on the R ¹ radical.

In further configurations of the invention, the embodiments mentioned above as preferred are modified in that the thiol groups are replaced by amino groups, preferably primary amino groups. It should be noted that these only react with C=C groups analogously to a thiol-ene reaction if the double bond of the reaction partner is in an activated form, for example as an acrylic or methacrylic group (e.g. as a (meth)acrylate group).

As a rule, the thiol addition is carried out in the presence of an initiator, as is known from the prior art, while the amine addition can also be carried out without an initiator.

The silanes of the formula (1) can be obtained in various ways. For example, they can be prepared by using a silane of the formula R ^x _a SiR _4-a (3), where a and R are as defined for formula (1) and R ^x R ³ is COO ^- where R ^{3 is} C ₁ -C ₆ -alkyl, preferably methyl, is reacted with a compound R ¹ -OH, in which R ¹ has the meaning given for formula (1). Depending on the used

Amount ratios one or more of the acyl groups R ³ COO ^- displaced by R ¹ -O-.

It is favorable if both the radicals R ^x and the radicals R are acyl radicals, for example acetyl radicals. The addition of two moles of R ¹ OH per mole of silane having four acyl radicals results in a mixture having an average of two R ¹ radicals per silane atom.

The silanes according to the invention or mixtures of these silanes can be inorganically condensed, for example via a hydrolysis reaction. This produces an inorganically crosslinked condensate (organically modified silicic acid polycondensate) with many thio or amino groups, which combines with compounds containing C=C double bonds or ring-containing compounds that are attacked by thiols or amines with ring opening to form an inorganically and organically crosslinked product ( Polymer) can be further implemented. In a specific embodiment, either other known, hydrolytically condensable silanes and/or alkoxy compounds of heteroatoms such as B, Al, Zr, Zn or Sn are added to the silanes according to the invention during the hydrolysis reaction. If alkoxy compounds of heteroatoms are added, the condensate can also be referred to as an organically modified silicic acid heteropolycondensate. If such additives are missing, a silicic acid homopolycondensate is formed. The term "silicic acid polycondensate" is intended to include both hetero- and homo-condensates.

As defined above, each member of the hydrocarbyl chain of R ² must have no more than 8 consecutive carbon atoms, but preferably less. If the total is 8 or less than 8, the presence of a cleavable group is optional. If the number is greater, there must be cleavable groups which interrupt the elements of the hydrocarbon-containing chain in such a way that no more than 8, but preferably even fewer, carbon atoms follow one another. Even with a total of at most 8 carbon atoms in the hydrocarbon-containing chain, this can optionally be subdivided into smaller elements by cleavable groups. In the event that the hydrocarbon skeleton of R ² has more than one hydrocarbon-containing chain (eg when compound (2) is a silane or a siloxane, ie a silicic acid polycondensate), this condition applies to each of the chains present . The shorter the element or elements made up of chains containing hydrocarbons, the better the degradability, because the shorter fragments are formed during degradation.

The hydrocarbon skeleton of R ² preferably has mainly or exclusively alkylene units. Their members can, but do not have to, be substituted with one or more substituents, the substituents preferably being selected from hydroxyl, carboxylic acid, phosphate, phosphonic acid, phosphoric acid ester, tertiary amino and amino acid groups. The hydrocarbon skeleton of R ² can consist of such alkylene units.

The hydrocarbon-containing chain of R ² can be further interrupted within the single element or elements by oxygen atoms (ether groups), sulfur atoms (thioether groups) or sulfonyl groups (-S(O) ₂ -).

The cleavable groups of R ² can be hydrolyzable, ie hydrolytically cleavable groups. These include, for example, the ester and anhydride groups and, as a rule, the ketal, acetal, disulfide, imine, hydrazone and oxime groups. Cleavable groups which are enzymatically cleavable such as the ester, amide, carbonate and carbamate groups can also be used. However, the groups can also be both hydrolytically and enzymatically cleavable. If the groups mentioned can also be cleaved in other ways, this is of course favorable according to the invention, since other cleavage reactions then open up for the degradation. Ester groups are preferred among the cleavable groups.

The thiols or amino groups of the silanes (1) or of the condensates formed therefrom or with it by hydrolysis ("silicic acid polycondensates") enter into an addition reaction in the manner of a thiol-ene reaction with the groups X of the compound (2).

worin R* und R** unabhängig voneinander H oder ein (ggf. funktionalisierter) organischer Rest sein können, R² weiterhin ein organischer Rest sein kann, der C=C-Gruppen enthält, und Z eine Sauerstoffbrücke oder den Rest -(CHR¹)-_n bedeutet, wobei R¹ H oder ein (ggf. funktionalisierter) organischer Rest ist und n 1, 2, 3, größer 3 bis etwa 20 oder sogar noch größer sein kann.In a first embodiment of the invention, the groups X have terminal polyaddable CC groups. These can be, for example, acrylic or methacrylic groups (eg acrylate and/or methacrylate groups), allyl ester, vinyl ester, allyl ether, vinyl ether, propenyl ether, maleimide or N-vinyl amide groups. These groups also include cycloolefinic, preferably bicycloolefinic and particularly preferably unsubstituted or substituted norbornenyl groups, preferably of the following formula:

wherein R* and R** can independently be H or an (optionally functionalized) organic radical, R ² can further be an organic radical containing C=C groups, and Z is an oxygen bridge or the radical -(CHR ¹ )- _n is where R ¹ is H or an (optionally functionalized) organic radical and n can be 1, 2, 3, greater than 3 to about 20 or even greater.

In an alternative configuration of the groups X, these are ring-opening systems. This includes, for example, epoxy groups and reactive cyclic ether groups with, for example, 4 ring members (oxetane group). The glycidyl or oxetane group can are unsubstituted or substituted. Furthermore, cyclic carbonate groups, such as those in the DE 4423811.8 are described, spiroesters / spiroorthoesters (the latter are for example in DE 4125201.2 shown) as well as spiroorthocarbonates and bicyclic orthoesters are used.

As mentioned, the compounds (2) can be purely organic compounds (preferably monomers or oligomers). Examples are esterified with at least two methacrylate diols or triols such as glycerol and their reaction products with dicyclopentadiene. Alternatively, at least one hydrolyzable silyl group can be integrated into the hydrocarbon structure of (2). This means that (2) can be a silane which essentially or exclusively has radicals bonded to the silicon via oxygen, of which at least two carry the group X mentioned or of which at least one carries two of the groups X mentioned , or it is possible to use corresponding hydrolytic condensates (silicic acid polycondensates) from silanes which also have radicals bonded to the silicon essentially or exclusively via oxygen. These polycondensates can then generally carry a total of more than two X groups, for example about one or two X groups per silicon atom; however, more or less is of course also possible. In this context, the silanes and silane condensates are particularly suitable WO 2016/037871 called, the C = C double bonds and carry in particular (meth) acrylic groups.

If a not yet hydrolytically condensed silane (1) is reacted with the compound (2) and/or the compound (2) is a not (yet) hydrolytically condensed silane, then after the reaction of (1) with (2) preferably a subsequent hydrolytic condensation. The rule, however, is that one starts with hydrolytically condensed silanes (1), ie a material that is already inorganically crosslinked, and reacts these either with a purely organic compound (2) or with a hydrolytic condensate of a silane of the formula (2).

The ratio between the groups X of the compound (2) and the thiol or amino groups of the silanes (1) or the silane condensates formed therefrom is variable. The groups are preferably used in a ratio of 1:1 or the thiol or amino groups are used in less than the X groups. The latter is favorable, for example, when the groups X are capable of homopolymerization, ie are, for example, (meth)acryl groups. Then, in addition to the addition reaction of the thiol or amino groups, a homopolymerization reaction of the groups X takes place at the same time--even if only to a minor extent. However, the groups X of the compound (2) can also be added in less than one amount. The ratio of the groups X of the compound (2) to the sum of the thiol and amino groups of the silanes (1) and any silane condensates formed therefrom can be from 0.1 to less than 1.0, preferably from 0.2 to 0.9. Alternative ratios are 0.5 to 0.9 or 0.1 to 0.5. To this This avoids unreacted crosslinking agent, which is toxic in the case of acrylate, remaining in the reaction mixture and possibly having to be removed. In addition, in this case there are unreacted groups of the silanes (1) which can be polyadded, namely thiol or amino groups, which, because of their polarity, promote, for example, the attachment of cells or are suitable for the covalent attachment of other molecules. The groups of the silanes (1) which can be polyadded thereby become functional groups in the organically modified, polymerized silicic acid polycondensate.

Curing through the thiol-ene reaction can occur via two different mechanisms: free radical thiol-ene reaction and thio-Michael addition. The free radical mechanism is initiated by a free radical initiator (thermal and/or photoinduced and/or redox induced). In particular, unactivated C=C double bonds (e.g. vinyl, allyl, norbornenyl groups) are suitable for this type of initiation. In order to also be able to initiate a thiol-Michael addition (particularly in the case of activated C=C double bonds, such as (meth)acrylate groups) locally and/or in terms of time, photobases can be used, since the thiol-Michael addition base-catalyzed. Photobases release a base upon exposure to light and can thus initiate the thiol-Michael addition. Photobases can therefore also be used in the preparation of the polymerized compounds according to the invention. The production and use of photobases is described in the literature.

If work is carried out photochemically, the irradiation can be carried out with visible and/or UV light. Combinations of different reactions, for example photochemical and thermal or a combination of redox-induced curing with, for example, photo-induced or thermal curing are also possible. Possible processing methods for structured materials are, for example, 2- or multi-photon polymerisation (2PP/MPP), digital light processing (DLP) and stereolithography (STL), although this list should not be taken as exhaustive. If the reaction is carried out appropriately (avoidance of an excess of compound (2) if this should be purely organic), only products are obtained which are monomer-free and therefore cannot be allergenic.

The polymerization reaction can take place from a (usually liquid or pasty) resin mass (in bulk form) that contains the components. For structured products such as scaffolds or implants - but not only for these - the polymerisation can take place in a bath, for example, in which the resin material is presented as a mass (liquid or pasty) and polymerised in a desired shape or a desired pattern (VAT polymerisation ). For this purpose, an exposure is preferably carried out with laser light in a known manner, for example a 2- or multi-photon polymerization ("TPA processing"), as for example in WO 2011/098460 A1 described. Instead, of course, a structuring with others VAT polymerization techniques are used, for example by the so-called DLP process, in which the desired shape is built up in layers by sequential exposure to light. The component adheres to a construction platform that hangs upside down in the resin mass. The bath with the resin mass is irradiated from below and the resulting component is lifted up layer by layer. The unpolymerized material can then be washed away. If a printing technique such as Multi Jet Modeling (MSM), Poly Jet Printing (PJP), Ink Jet is used, only the required material is printed in layers, so that washing out is not necessary.

If scaffolds are to be produced, the pores required for the growth of the biological material can be produced directly in the shaped body with the aid of the structuring techniques mentioned. With DLP, pores can be created primarily in the µm range, with TPA also below that, i.e. in the nm range.

The compounds according to the invention, ie the silane, the organically modified silicic acid polycondensate and the organically modified, polymerized silicic acid polycondensate, can therefore also be used to produce framework structures (scaffolds). Thus, the shaped body that can be produced according to the invention can also be a framework structure.

Depending on the number of radicals R ¹ and R ² , the reaction of (1) with (2) gives rise to a product which may be in the form of a chain or ring, but is usually crosslinked (hybrid polymer). Depending on the cleavable groups selected, this can usually be degraded in different ways, but of course in particular hydrolytically or enzymatically, due to the fact that both components (1) and (2) usually only have short hydrocarbon chains, which may be corresponding hydrolytically or enzymatically and optionally otherwise cleavable groups are separated from one another. Instead or in addition, the hydrocarbon-containing chains remaining when the cleavable groups are cleaved can be water-soluble—at least at the temperature of the human body, but preferably at normal ambient temperature, ie about 25.degree. When stored in buffers, the hybrid polymers decompose to a greater or lesser extent within a few weeks, with the formation of toxically harmless, mostly water-soluble, small-scale degradation products. Both the organic network structure and the oxygen bridge between the organic substituent and the silicon atom are also cleaved. The hybrid polymers according to the invention are therefore suitable for the production of completely biodegradable or resorbable implants or scaffolds with mechanical data adapted to the respective intended use. The silanes and hybrid polymers according to the invention are also suitable for use in bone cements.

The materials obtained in this way, as well as some of their precursors, are—in contrast to some materials such as (meth)acrylate materials—stable to irradiation with γ rays (preferred method due to ease of use) so that they can be sterilized. Sterilization of the shaped bodies produced is often essential, especially in the medical field, for example if they are to be used as bone substitutes or scaffolds. And not only the fully polymerized products of the invention can be sterilized, but also the silanes/silicic acid polycondensates (1) and many crosslinkers (2), so that the starting materials for the crosslinked products can be sterilized without further ado.

By varying the proportion of inorganically crosslinkable units and/or of organically polymerizable/polyaddable units, the mechanical properties of the hybrid polymers produced from the silanes can be specifically adjusted so that they resemble those of natural, soft or hard tissue. They can be colonized by cell types such as endothelial cells and are therefore suitable, for example, as scaffolds for stabilizing and growing cells.

The invention is to be explained in more detail below using a schematic representation of a silane of the formula (1) according to the invention. Shown is one of the substituents R ¹ on the silane (1) bonded to the silicon atom through an oxygen atom. Here, this oxygen atom is part of a glycerol unit. The two remaining alcohol groups of these units are esterified with thioglycolic acid groups. The group is thus branched and has thiol groups at its ends remote from the silicon atom, which are organic with a compound containing two or more CC double bonds or rings (hereinafter generally referred to as "multi-ene") in the sense of a thiol-ene polyaddition can be networked.

The two exemplary carboxylic acid ester groups present in this group are susceptible to hydrolysis and are referred to here as DG. Takes place under hydrolysis conditions also the cleavage of the Si-O bond. This provides a material that is degradable to silicon at the point of attachment of the organic group.

The associated crosslinking component (2) is shown below in general form and as an example for a multi-ene.

In this case, the multi-ene contains two hydrolytically cleavable carboxylic acid ester groups, which are in turn denoted here by DG. There are also two terminal methacrylate groups.

The organic polymerization leads to the organic crosslinked structure below.

One recognizes from the above explanations immediately that the provision of only short, optionally by oxygen atoms, sulfur atoms, ester, amide, carbonate, carbamate, ketal, acetal, disulfide, imine, hydrazone and / or Oxime groups interrupted hydrocarbon chains in hydrolytic / enzymatic / etc. Degradation to small molecular products leads, which are usually physiologically harmless as such. In this way, the entire organic part of the hybrid polymer can be broken down into small-molecular products. In the example above, for example, glycerol and a dicarboxylic acid containing a thioether are formed, which are toxicologically harmless. The remaining, essentially inorganic residues are likely to be essentially fragments with Si-O-Si linkages which are outwardly covered with hydroxy groups.

The material properties of the hybrid polymers according to the invention can be influenced in many ways by the incorporation of additives, such as fillers, prior to the organic crosslinking. Fillers of various shapes that are themselves degradable or degradable are particularly suitable here, such as tricalcium phosphate, hydroxyapatite, magnesium particles or bioglass (particles made up of a glass base of, for example, SiO ₂ , Na ₂ O or K ₂ O/CaO/ Phosphorus compounds such as P ₂ O ₅ which gradually dissolve under certain environmental conditions, see Bioactive Glasses, Fundamentals, Technology and Application by Royal Society of Chemistry ). With such fillers and other additives, the degradation behavior, mechanical properties such as mechanical stability (e.g. by increasing the modulus of elasticity, etc.), the osteoconductivity and - inductivity (e.g. in bone scaffolds), the biocompatibility and / or the generation of affect pores. Pores can be created either directly, by appropriate structuring of the shaped body, or by containing degradable or degradable fillers in the organically crosslinked material, which quickly degrade after the shaped body, such as a scaffold, has been inserted into the body. A local acceleration of the degradation can also be achieved, for example, by using a filler which supplies basic degradation products when it decomposes. Bioglasses, for example, are suitable as fillers for this purpose. Of course, non-degradable fillers can also be added in order to influence, in particular to increase, the mechanical stability of a molded article produced from the material according to the invention. Of course, it is favorable if such fillers are in turn made up of small particles.

Photobases and photoacids can be integrated into the material systems as triggers in order to initiate degradation at a later point in time or to increase the degradation rate of a specimen by the acids or bases released by the exposure of the specimen catalyzing the cleavage of the degradable groups. The production and corresponding use of photobases and photoacids is described in the literature.

The use of photobases is advantageous since they can be used not only, as described above, in the synthesis of the compounds according to the invention but also in their degradation.

It is also possible to add proteins to the material according to the invention which have the properties of growth factors (eg bone morphogenic proteins) or osteoinductive ones Possess mediators to further improve the suitability of the material as a scaffold in tissue engineering. Such proteins can be used as an additive or directly attached to components (1) and/or (2) and thus as their constituents, although in the latter case the conditions specified for them must of course be observed (e.g. binding of the proteins via an ester group; linkage of the individual amino acids via acid amide groups).

The use of the materials according to the invention extends i.a. for use in the form of bulk materials, fibers, composites, cements, adhesives, casting compounds, coating materials, use in (reaction) extruders, in the field of multi-photon polymerisation. They are suitable for a wide variety of purposes. Use for medical applications (eg as an implant, bone replacement material, bone cement) is of particular importance. However, use in other areas of application outside the body is also possible.

The invention will be explained in more detail below using examples.

A. Preparation of a compound R ¹ -OH (S ₃ ):

To 18.00 g (155.01 mmol, 1.0 equiv) of 2-hydroxyethyl acrylate (HEA) was added 0.07 g (0.06 wt%) of 1,5-diazabicyclo[4.3.0]non-5 -en given (DBN). 104.32 g (496.04 mmol, 3.2 equiv.) Glycol dimercaptoacetate (GDMA) were then added dropwise with stirring and the reaction mixture was stirred at room temperature for 24 h. The resulting product mixture was purified by column chromatography (dichloromethane/ethyl acetate 10:1) and the desired product HEA-GDMA (S3) was obtained in a yield of 38.01 g (74%).

B. Preparation of silanes of formula (1) B1 Transesterification of a compound R ¹ -OH (here: HS-CH ₂ -CH ₂ -OH, S ₁ ) with a silane of formula (3) (here Si(OAc) ₄ ) to a silane of formula (1) (product U ₁ ):

37,33 g (141,26 mmol, 1,0 Äquiv.) Siliciumtetraacetat wurden mit 30,00 g (282,51 mmol, 2,0 Äquiv.) S1 (2-Mercapto-3-butanol), versetzt. Diese Reaktionsmischung wurde zunächst 1 min bei Raumtemperatur gerührt und daraufhin 1,5 h bei 15 mbar auf 50 °C erhitzt. Danach wurde der Druck für weitere 1,5 h auf 1 mbar reduziert. Das Reaktionsgemisch wurde 8 h im Ölpumpenvakuum von flüchtigen Bestandteilen befreit und mit Hilfe von Druckluft über einen Filter mit 15 µm Porengröße filtriert. Bei dem entstehenden Produktgemisch U1 sind durchschnittlich zwei Alkoxygruppen und zwei Acetoxygruppen an ein Siliciumatom gebunden. Ausbeute: 49,62 g (99 %)

To 37.33 g (141.26 mmol, 1.0 equiv) of silicon tetraacetate was added 30.00 g (282.51 mmol, 2.0 equiv) of S1 (2-mercapto-3-butanol). This reaction mixture was first stirred at room temperature for 1 min and then heated at 50° C. at 15 mbar for 1.5 h. The pressure was then reduced to 1 mbar for a further 1.5 h. The reaction mixture was freed from volatile constituents in an oil pump vacuum for 8 h and filtered using compressed air through a filter with a pore size of 15 μm. In the resulting product mixture U1, on average two alkoxy groups and two acetoxy groups are bonded to a silicon atom. Yield: 49.62 g (99%)

B2. Transesterification of a compound R ¹ -OH (here: trimethylolpropane-di(1-mercapto-ethyl ester), S ₂ ) with a silane of the formula (3) (here Si(OAc) ₄ ) to give a silane of the formula (1) (product U ₂ ):

27,49 g (104,04 mmol, 1,0 Äquiv.) Siliciumtetraacetat wurden mit 50,00 g (208,07 mmol, 2,0 Äquiv.) S2 (Isomerengemisch) versetzt. Diese Reaktionsmischung wurde zunächst 1 min bei Raumtemperatur gerührt und daraufhin 10 min bei 50 mbar auf 80 °C erhitzt. Danach wurde der Druck für weitere 2,5 h auf 1 mbar reduziert. Das Reaktionsgemisch wurde 8 h im Ölpumpenvakuum von flüchtigen Bestandteilen befreit und mit Hilfe von Druckluft über einen Filter mit 15 µm Porengröße filtriert. Bei dem entstehenden Produktgemisch U2 sind durchschnittlich zwei Alkoxygruppen (basierend auf unterschiedlichen Anteilen der Isomeren von von S2) und zwei Acetoxygruppen an ein Siliciumatom gebunden. Ausbeute: 63,80 g (98 %). Es ist anzumerken, dass das Mischungsverhältnis der Isomeren von S₂, im Beispiel 1,56:0,44 Mol, beliebig gewählt werden kann.

To 27.49 g (104.04 mmol, 1.0 equiv) of silicon tetraacetate was added 50.00 g (208.07 mmol, 2.0 equiv) of S2 (mixture of isomers). This reaction mixture was first stirred at room temperature for 1 min and then heated to 80° C. at 50 mbar for 10 min. The pressure was then reduced to 1 mbar for a further 2.5 hours. The reaction mixture was freed from volatile constituents in an oil pump vacuum for 8 h and filtered using compressed air through a filter with a pore size of 15 μm. The resulting product mixture U2 has an average of two alkoxy groups (based on different proportions of the isomers of S2) and two acetoxy groups attached to one silicon atom. Yield: 63.80 g (98%). It should be noted that the mixing ratio of the isomers of S ₂ , in the example 1.56:0.44 mol, can be chosen arbitrarily.

B3. Transesterification of a compound R ¹ -OH (here: compound from preparation A, S ₃ ) with a silane of the formula (3) (here Si(OAc) ₄ ) to give a silane of the formula (1) (product U ₁ ):

13,76 g (52,08 mmol, 1,0 Äquiv.) Siliciumtetraacetat wurden mit 34,00 g (104,17 mmol, 2,0 Äquiv.) S3 versetzt. Diese Reaktionsmischung wurde zunächst 1 min bei Raumtemperatur gerührt und daraufhin 15 min bei 15 mbar auf 80 °C erhitzt. Danach wurde der Druck für weitere 3 h auf 1 mbar reduziert. Das Reaktionsgemisch wurde 8 h im Ölpumpenvakuum von flüchtigen Bestandteilen befreit und mit Hilfe von Druckluft über einen Filter mit 15 µm Porengröße filtriert. Bei dem entstehenden Produktgemisch U3 sind durchschnittlich zwei Alkoxygruppen und zwei Acetoxygruppen an ein Siliciumatom gebunden. Ausbeute: 34,55 g (98 %).

To 13.76 g (52.08 mmol, 1.0 equiv) of silicon tetraacetate was added 34.00 g (104.17 mmol, 2.0 equiv) of S3. This reaction mixture was first stirred at room temperature for 1 min and then heated to 80° C. at 15 mbar for 15 min. The pressure was then reduced to 1 mbar for a further 3 hours. The reaction mixture was freed from volatile constituents in an oil pump vacuum for 8 h and filtered using compressed air through a filter with a pore size of 15 μm. In the resulting product mixture U3, an average of two alkoxy groups and two acetoxy groups are bonded to a silicon atom. Yield: 34.55 g (98%).

C. Hydrolysis + Condensation - Production of the resins H1, H2 and H3:

The product mixtures U1, U2 and U3 were then each hydrolyzed at 90 °C in several steps. To this end, enough water was added that there is one water molecule for every fifth remaining bonded acetoxy group (but at least one water molecule for every twentieth acetate group present before hydrolysis). After the water had been added, the mixture was stirred at 90° C. for 1 min and the volatile constituents were then removed under an oil pump vacuum. The degree of hydrolysis of the Si—OAc and Si—OAlk groups was checked in each case by means of ¹ H NMR spectroscopy. The water addition was repeated until essentially all acetate groups were removed from the mixture. No cleavage of the alkoxy groups was observed here. The resulting products H1, H2 and H3 have on average two alkoxy groups attached to one silicon atom. The respective products are described below as SH resins H1, H2 and H3.

SH resin systems:

• H1 (has on average two alkoxy groups and two (OH/O...) groups per Si atom)
  
• H2 (has on average two alkoxy groups and two (OH/O...) groups per Si atom)
  
• H3 (has on average two alkoxy groups and two (OH/O...) groups per Si atom)
  

D. Preparation of the crosslinkers (compounds (2)) D1.

0.012 g (0.04% by weight) of butylated hydroxytoluene (BHT) is dissolved in 30.00 g (131.44 mmol) of glycerol dimethacrylate (mixture of mono-, di- and trisubstituted glycerol; on average disubstituted). The reaction mixture is then stirred at 80° C. and cyclopentadiene is slowly added dropwise. The cyclopentadiene is produced in parallel by the thermal cleavage of dicyclopentadiene and transferred into the reaction mixture by distillation. Conversion of the methacrylate group is monitored by ¹ H NMR spectroscopy. After completion of the reaction, unreacted cyclopentadiene and dicyclopentadiene are removed from the reaction mixture under reduced pressure. Yield: 47.31 g (100%). If, as in the above example, a mixture of different isomers of glycerol dimethacrylate is used, corresponding isomer mixtures of V ₁ result. These can be represented as follows:

In the exemplary case, the proportions of the isomers of the glycerol dimethacrylate (and accordingly also those of the product isomers) (read from top to bottom) were 18, 49, 16, 16 and 1 mole %. It is of course also possible to use other isomer ratios or mixtures or pure isomers.

0.012 g (0.04% by weight) of butylated hydroxytoluene (BHT) is dissolved in 30.00 g (104.78 mmol) of triethylene glycol dimethacrylate. The reaction mixture is then stirred at 80° C. and cyclopentadiene is slowly added dropwise. The cyclopentadiene is produced in parallel by the thermal cleavage of dicyclopentadiene and transferred into the reaction mixture by distillation. Conversion of the methacrylate group is monitored by ¹ H NMR spectroscopy. After completion of the reaction, unreacted cyclopentadiene and dicyclopentadiene are removed from the reaction mixture under reduced pressure. Yield: 43.25 g (100%).

z.B. mit M_n = 575 g/mol d.h. im Schnitt n = 10 - 11, oder mit M_n = 700 g/mol).

D3. Further examples of crosslinkers, some of which can be produced in a manner comparable to V ₃ , are:

eg with M _n = 575 g/mol ie on average n = 10 - 11, or with M _n = 700 g/mol).

Because the norbornenyl groups of the above di-norbornenyl compounds are attached to the polyglycol via carboxylic acid groups or carbonate groups, a water-soluble hydrocarbon-containing chain is formed in each case during the hydrolysis. Such crosslinkers are therefore suitable according to the invention as component (2). The water solubility of the degradation products can also be achieved by means of hydroxyl groups (see the lowest of the crosslinkers above).

D4. Examples of crosslinkers with C=C double bonds allyl ether:

vinyl ester:

allyl esters:

Other crosslinkers:

E. Curing of the resin systems/specimen preparation and characterization E1 Mechanical investigations:

tensile modulus of elasticity tensile strenght H2 + V2 ~ 35Mpa ~1.6MPa H1 + V1 ~ 1900MPa ∼17MPa

It can be seen that the materials according to the invention can be used to bring about a specifically sought-after adaptation of the mechanical values to certain tissues. Since both the inorganic and the organic crosslinking density can be adjusted, the person skilled in the art can achieve precisely the desired values by making a suitable choice within the parameters that the invention describes.

E2. degradation attempts Sample preparation:

0.04 g of 1,5-diazabicyclo[4.3.0]non-5-ene was dissolved in 4.77 g of V2. After the addition of 5.50 g H2, the specimens (diameter 10 mm; height 2 mm) were cured in an oven at 100 °C for 1 hour.

0.10 g Lucerin-TPO and 0.02 g pyrogallol were dissolved in 5.55 g V1. After the addition of 4.00 g H1, the test specimens (diameter 10 mm; height 2 mm) were cured by exposure to light (2×5 min).

Mass loss + water absorption:

The specimens were stored in distilled water or in buffer solutions (phosphate buffer and carbonate buffer) at 37°C. The degradation medium was renewed every 5-7 days. The weight loss of the samples was determined after 16 weeks.

The following weight loss was observed:

sample degradation medium Weight loss after 16 weeks V2 + H2 dist. _H2O 28% V2 + H2 phosphate buffer 20% V2 + H2 carbonate buffer 100% V1 + H1 dist. _H2O 5% V1 + H1 phosphate buffer 3% V1 + H1 carbonate buffer 6%

The degradation rate is strongly dependent on the pH value of the degradation medium and the network structure of the material system used and can be set accordingly and adapted to the requirements.

The following water uptake was observed:

sample degradation medium Water intake after 16 weeks V2 + H2 dist. _H2O 50% by weight based on dry weight V2 + H2 phosphate buffer 100% by weight based on dry weight V2 + H2 carbonate buffer 54% by weight based on dry weight (after 4 weeks; completely degraded after 16 weeks) V1 + H1 dist. _H2O 10% by weight based on dry weight V1 + H1 phosphate buffer 7% by weight based on dry weight V1 + H1 carbonate buffer 14% by weight based on dry weight

The water absorption correlates with the above mass loss and the dependencies described.

A comparison of the two examples above shows that the water absorption can be varied by choosing suitable compounds/condensates (1) and (2). Thus, replacing V2 with V1 (replacing the methacrylate groups with norbornenyl groups) leads to greater hydrophobicity of the product. At the same time, replacing the resin H2 with H1 reduces the distance between the SH groups and the Si atoms and thus increases the crosslinking potential. Both effects are likely to contribute to the observed reduction in water uptake.

→ ¹ H-NMR investigations:

V2 + H2: The degradation media were examined using ¹ H-NMR spectroscopy in order to identify possible degradation products. The cleavage of the Si-OC bond between the organic and inorganic network could be demonstrated. The hydrolytic cleavage of all other predetermined breaking points (ester groups in the exemplary embodiments listed) could also be confirmed by the detection of glycerol in the degradation media.

V1 + H1: The degradation media were examined using ¹ H-NMR spectroscopy in order to identify possible degradation products. The cleavage of the Si-OC bond between the organic and inorganic network could be demonstrated.

F. 3D printing using digital light processing (DLP method)

The degradable inorganically pre-crosslinked silanes described, for example H1, H2 and/or H3, can be additionally organically crosslinked with the crosslinkers described, for example V1, V2 and/or V3, through the photoreactive groups and thus cured. This enables the processing of the described material in a 3D printer, which is based on the DLP principle. Individual structures can be created.

Application example 1:

0.26 g Lucirin-TPO and 0.052 g pyrogallol are dissolved in 16.12 g V3. After the addition of 10.00 g H1, the material could be processed in a Rapidshape S60-LED 3D printer (DLP process) and the desired shape produced. The shaped body produced in this way is in Fig.1 shown.

The example was repeated, with 0.5% by weight of titanium oxide nanoparticles being added as a filler. The porous shaped body produced in this way (in 2 shown) is suitable, for example, as a bone replacement material.

Application example 2 - 3D printed component made of degradable hybrid polymer Material system used:

• H1 + V3
• + 1% by weight LUCIRINO TPO (initiator)
• + 0.05% by weight of pyrogallol
• + 1% by weight TiO ₂ nanoparticles

LUCIRINO TPO and pyrogallol were dissolved in V3, then H1 was added and mixed homogeneously. The TiO ₂ nanoparticles were then incorporated using a speed mixer (DAC 150 FVZ, Hauschild Engineering, Hamm) at 2000 rpm for 3 minutes.

3D printer used:

Rapidshape S60 LED (DLP principle)

Processing parameters when printing:

• Burn factor: 300%
• Baking gradient: 7 layers
• Pushing force: -50.0mN/ ^mm2
• Separating force: 40.0 mN/ ^mm2
• Separation distance: 500 µm
• Energy: 1500.0 mJ/ ^dm2

The material system was processed in the 3D printer mentioned to form a lattice cube with an edge length of 1 cm and interconnected pores.

Claims (13)

1. A silane of the formula (1)
   
           R¹ _aSiR_4-a     (1),
   
   wherein

   the group R¹ or each of the groups R¹ independently

   - is bound to the silicon via an oxygen atom,

   - has a straight or branched hydrocarbonaceous chain containing a plurality of chain sections each having not more than 8 consecutive carbon atoms, wherein the hydrocarbonaceous chain is composed of alkylene units the members of which are unsubstituted or substituted, wherein the substituents are selected from hydroxy, carboxylic acid, phosphate, phosphonic acid ester, phosphoric acid ester, tertiary amino and amino acid groups, and the hydrocarbonaceous chain is further substituted within each element by oxygen atoms, sulphur atoms or sulphonyl groups, wherein each of the chain sections of the hydrocarbonaceous chain is separated from the next chain section by an ester group as a cleavable group,

   - has at least one thiol or a primary or secondary amino group,

   the group R or each of the groups R is independently a hydrolytically condensable group selected from alkyl-COO-, alkyl-O- and HO-, and

   a is 1, 2, 3 or 4.
2. The silane of the formula (1) according to claim 1, in which at least one of the chain sections of the hydrocarbon skeleton of the radical R¹ has a maximum of six consecutive carbon atoms.
3. An organically modified silica polycondensate comprising a hydrolytic condensation product of a silane according to claim 1 or 2 or a mixture of a plurality of said silanes.
4. An organically modified, polymerized silicic acid polycondensate preparable by reacting the silane of the formula (1) according to claim 1 or 2 and/or an organically modified silicic acid polycondensate according to claim 3 with a compound R²(X)_b (2),
   wherein

   the group R² comprises a b-fold binding hydrocarbon backbone with a straight or branched hydrocarbonaceous chain having one or more chain sections each having not more than 8 consecutive carbon atoms, each of a plurality of chain sections of the hydrocarbonaceous chain being separated from the next chain section by a cleavable group,
   wherein the cleavable groups are selected from ester, anhydride, amide, carbonate, carbamate, ketal, acetal, disulfide, imine, hydrazone and oxime groups,

   X is a group which, in the said reaction, undergoes an addition reaction with the at least one thiol or primary or secondary amino group of the radical R¹ of the silane of formula (1), and

   b is 2, 3, 4 or greater 4.
5. The organically modified polymerized silica polycondensate according to claim 4, which is the product of the reaction of the silane of formula (1) according to claim 1 or 2 with said compound (2), said product having been subjected to hydrolytic condensation after said reaction.
6. The organically modified polymerized silica polycondensate according to claim 4 or 5, wherein the chain section or at least one of the chain sections of the hydrocarbonaceous chain of the radical R² has one or both of the following features (i) and (ii):

   (i) it is composed of alkylene units, the alkylene units being unsubstituted or at least one of the alkylene units being substituted with one or more groups selected from hydroxy, carboxylic acid, phosphate, phosphonic acid, phosphoric acid ester and tertiary amino and amino acid groups

   (ii) it is interrupted by one or more oxygen atoms and/or sulphur atoms and/or sulphonyl groups.
7. The organically modified, polymerised silicic acid polycondensate according to claim 6, wherein at least one of the chain sections of the hydrocarbonaceous chain of the radical R² (i) has at least one of the substituted alkylene units and (ii) is interrupted by one or more oxygen atoms and/or sulphur atoms and/or sulphonyl groups.
8. The organically modified polymerized silica polycondensate according to any one of claims 4 to 7, wherein the group X of compound (2) has at least one organically polymerizable C=C double bond as a constituent of a group selected from an acrylate, or methacrylate or norbornenyl group, or an epoxy ring or spiro group.
9. The organically modified polymerized silica polycondensate according to any one of claims 4 to 8, wherein at least one of the chain sections of the hydrocarbonaceous chain of the radical R² has both of the following features (i) and (ii):

   (i) it is composed of alkylene units, at least one of the alkylene units being substituted with one or more groups selected from hydroxy, carboxylic acid, phosphate, phosphonic acid, phosphoric acid ester and tertiary amino and amino acid groups

   (ii) it is interrupted by one or more oxygen atoms and/or sulphur atoms and/or sulphonyl groups.
10. The organically modified polymerized silica polycondensate according to any one of claims 4 to 9, wherein the compound R²(X)_b has a molecular weight of at most 3000 g/mol.
11. The organically modified polymerized silica polycondensate according to any one of claims 4 to 10, wherein the ratio of the groups X of compound (2) to the sum of the thiol and amino groups in the silanes (1) and condensation products thereof is 0.1 to below 1.0.
12. The organically modified polymerized silica polycondensate according to any one of claims 4 to 11 in the form of a shaped body.
13. The use of the shaped body according to claim 12 as a biologically or medically useful object or as an object for cell or tissue stabilization or for cell or tissue cultivation.

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